Risk Factors For Early-onset Neonatal Sepsis Research Articles

Umbilical Cord Blood Culture as an Aid to the Diagnosis of Early Onset Neonatal Sepsis: A Cross-sectional Study

Introduction: Neonatal sepsis is one of the leading causes of neonatal morbidity and mortality globally, accounting for an estimated neonatal mortality rate of 23.9 per 1000 live births. Due to overlapping signs and symptoms, a specific diagnosis of sepsis poses a diagnostic challenge. Blood collected from a peripheral vein for sepsis screening and blood culture remains the gold standard for diagnosing neonatal sepsis. The umbilical cord is still not routinely used as a site for collecting blood for sepsis screening and blood culture. Aim: To determine the diagnostic efficacy of Umbilical Cord Blood Culture (UCBC) compared to Peripheral Venous Blood Culture (PVBC) in Early Onset Neonatal Sepsis (EONS). Materials and Methods: This cross-sectional observational study was conducted at the Neonatology Unit, Department of Paediatrics, Assam Medical College and Hospital (AMCH), Dibrugarh, Assam, India, involving 110 neonates with two or more risk factors for EONS over a one-year period (August 2021-July 2022). Umbilical cord blood and peripheral venous blood were collected and cultured, and the neonates were monitored throughout their hospital stay. Statistical significance was determined using the Chi-square test for categorical variables and the t-test for continuous variables (with a p-value <0.05 considered statistically significant). The validity of UCBC for diagnosing early neonatal sepsis was assessed based on sensitivity, specificity, Positive Predictive Value (PPV), and Negative Predictive Value (NPV). Results: The mean gestational age was 34.95±3.314 weeks and mean birth weight was 2.08±0.790 grams. Of the 110 high- risk neonates, sepsis screening was positive in 67 (61%), while UCBC and PVBC were positive in 19 (17.3%) and 10 (9.09%), respectively. Acinetobacter was the most common organism found in both cultures. The sensitivity and specificity of sepsis screening were 100% and 47.25% compared to UCBC and 90% and 42% compared to PVBC. In comparison to PVBC, UCBC demonstrated a sensitivity and specificity of 70% and 88%, with a diagnostic accuracy of 86.36%. Conclusion: The UCBC exhibits good diagnostic accuracy for diagnosing EONS and can be utilised due to it being a painless and technically less challenging method of blood sampling, with high sensitivity and specificity.

Tailored Approach to Evaluation and Management of Early Onset Neonatal Sepsis in a Safety-Net Teaching Hospital in Northeast Florida.

Objective Early onset neonatal sepsis (EONS) remains a significant cause of morbidity and mortality in newborns in the immediate postnatal period. High empiric antibiotic use in well-appearing infants with known risk factors for sepsis led the American Academy of Pediatrics (AAP) to revise its 2010 guidelines for the evaluation and management of EONS to avoid overuse of antibiotics. In this recent clinical report, the AAP provided a framework that outlined several evidence-based approaches for sepsis risk assessment in newborns that can be adopted by institutions based on local resources and structure. One of these approaches, the sepsis risk calculator (SRC) developed by Kaiser Permanente, has been widelyvalidated for reducing unnecessary antibiotic exposure and blood work in infants suspected of having EONS. In order to determine the utility and safety of modifying our institution's protocol to the SRC, we implemented a two-phased approach to evaluate the use of SRC in our newborn nursery. Phase 1 utilized a retrospective review of cases with SRC superimposition. If results from Phase 1 were found to be favorable, Phase 2 initiated a trial of the SRC for a six-month period prior to complete implementation. Methods Phase 1 consisted of retrospectively applying the SRCto electronic medical records (EMR) of infants ≥ 35 weeks' gestational age admitted to the newborn nursery with risk factors for EONS between June 2016 and May 2017. We compared actual antibiotic use as determined by the unit's EONS protocol for evaluation and management based on 2010 Centers for Disease Control and Prevention (CDC) and AAP guidelines to SRC-recommended antibiotic use. We used EMR to determine maternal and infant data, blood work results, and antibiotic usage as well asused daily progress notes by the clinical team to determine the clinical status of the infants retrospectively. Based on the projected reduction in blood work and antibiotics use with the retrospective superimposition of SRC on this cohort of infants and identification of our high-risk patient subset, we developed a novel, hybrid EONS protocol that we implemented and assessed throughout Phase 2, a six-month period from August 2018 to January 2019, as a prospective observational study. Results Phase 1 (SRC superimposition) demonstrated that the use of the SRC would have reduced empiric antibiotic use from 56% to 13% in the study cohort when compared with 2010 CDC/AAP guidelines. However, these same findings revealed use of the SRC would have resulted in delayed evaluation and initiation of antibioticsin 2 of 4 chorioamnionitis-exposed infants with positive blood cultures. During Phase 2 (n=302), with the implementation of our tailored approach (SRC implementation with additional blood culture in chorioamnionitis-exposed infants), 12 (4%) neonates received empiric antibiotic treatment compared to nine (3%) neonates who would have been treated per strict adherence to SRC recommendations. No neonate had culture-positive EONS. Continued use of 2010 CDC/AAP guidelines would have led to empiric antibiotic use in 38 (12.6%) infants in this cohort. Conclusion We developed a novel hybrid approach to the evaluation and management of neonates at increased risk of EONS by tailoring SRC recommendations to our safety-net population. Our stewardship effort achieved a safe and significant reduction in antibiotic usage compared to prior usage determined using CDC/AAP guidelines.

Diagnostic Accuracy of Haematological Scoring System in Paired cord Blood and Peripheral Venous Blood for early Detection of Neonatal Sepsis – A Prospective Analytical Study

Introduction: Sepsis is one of the major causes of neonatal morbidity and mortality. Early recognition and diagnosis of early onset neonatal sepsis (EONS) is difficult. Hence, there is a need for early predictive screening method for EONS, for which Haematological Scoring System (HSS) is used. It comprises of total leucocyte count, immature / total neutrophil ratio, total PMN count, immature PMN count, degenerative changes in PMN and platelet count.
 Methods: 100 inborn neonates with two or more risk factors for EONS, chosen by sequential sampling method were included in this prospective analytical study. Blood samples were collected from umbilical cord and peripheral vein and analysed for haematological parameters. Blood cultures were performed as gold standard for diagnosing neonatal sepsis and sepsis screen was done to corroborate the diagnosis of EONS.
 Results: Out of 100 neonates, 21 had sepsis, 14 had probable sepsis and 65 had no sepsis. Among the variables of HSS it was observed that elevated I:T ratio, thrombocytopenia, elevated I:M ratio and elevated immature neutrophil count have shown significant correlation with EONS with statistically significant p values (p value < 0.05), with raised I:T ratio being highly sensitive in identifying neonatal sepsis and degenerative changes in neutrophils being highly specific.
 Conclusions: The HSS was found to be satisfactory in identifying EONS. It can be used as a simple, quick, cost effective and readily available screening test with decent sensitivity and high specificity, for detection of EONS.

Procalcitonin levels in maternal serum and cord blood as marker for diagnosis of early onset neonatal sepsis.

To assess the diagnostic accuracy of Procalcitonin in maternal serum and umbilical cord blood samples to predict Early onset neonatal sepsis (EONS). It was a Prospective analytical cohort study. Pregnant women ≥34 weeks gestation in active labour, with risk factors for EONS were included in the study. Maternal blood samples at recruitment and umbilical cord blood samples after delivery were taken for Total leucocyte count (TLC), high sensitivity C-Reactive Protein (hs-CRP) and Procalcitonin. Newborns were classified into non-infected, suspected and proven infection. Sensitivity, specificity and diagnostic accuracy of maternal and cord blood procalcitonin, TLC and hs-CRP were calculated. A total of 200 women were recruited. Maternal procalcitonin had a superior diagnostic accuracy of 99% compared to maternal TLC and maternal hs-CRP. Also, cord blood procalcitonin had a diagnostic accuracy of 95%. Procalcitonin in both maternal as well as cord blood is a promising biomarker to detect EONS with high diagnostic accuracy.

Comparative microbial analysis and assessment of paired umbilical cord blood culture and peripheral venous blood culture in neonates with high risk factors to detect early onset neonatal sepsis: A study from tertiary care hospital of central India

Background: Neonatal sepsis is a prime cause of neonatal morbidity and mortality. Peripheral venous blood (PVB) culture is a gold standard for the diagnosis of neonatal sepsis. Low sensitivity of blood culture in newborn is due to small volume of blood sample and antibiotics given before sampling. Aims and Objectives: The study aims to compare and analyze the microbial spectrum in the Umbilical cord blood (UCB) culture with PVB culture and evaluation of both for detection of early onset neonatal sepsis (EONS) in high risk neonates and to use appropriate microorganism specific antibiotic for treating the sepsis. Materials and Methods: About 100 inborn neonates with two or more risk factors for EONS, chosen by sequential sampling method were included in this prospective analytical study. Blood samples were collected from umbilical cord and peripheral vein for culture. Sepsis screen was done to substantiate the diagnosis of neonatal sepsis. Results: Out of 100 neonates, 21 belongs to sepsis; 14 to probable sepsis; 65 to no sepsis. Among these 27 had UCB culture & 24 had PVB culture +ve. Organisms grown on culture were Klebsiella(m/c isolate), Staphylococcus aureus, Escherichia coli, Acinetobacter, Coagulase-ve Staphylococcus (blood culture contaminant), Pseudomonas and Enterococcus. Conclusion: UCB culture is simple and convenient method for the diagnosis of neonatal sepsis as compared to PVB culture with Sensitivity of 66% and specificity of 93%. Organisms grown are comparable to PVB culture sample (Klebsiella - most common isolate).

Comparative assessment of umbilical cord blood with peripheral venous blood using hematological scoring system as an early predictive screening method for the detection of early-onset neonatal sepsis in the tertiary care center of Central India

Background: Sepsis is one of the major causes of neonatal morbidity and mortality. Early recognition and diagnosis of early-onset neonatal sepsis (EONS) is difficult because of the variable and non-specific clinical presentation of this condition. Hence, there is a need for early predictive screening method for EONS. Aims and Objectives: To compare the umbilical cord blood Haematological Scoring System (HSS) with peripheral venous blood as an early predictive screening method for detection of EONS. Materials and Methods: 100 inborn neonates with two or more risk factors for EONS, chosen by sequential sampling method were included in this prospective analytical study. Blood samples were collected from the umbilical cord and peripheral vein analyzed for hematological parameters, sepsis screen, and peripheral smear for HSS of Rodwell et al., send for blood culture. Blood cultures were performed as gold standard for diagnosing neonatal sepsis and sepsis screen was done to corroborate the diagnosis of neonatal sepsis. Results: Of 100 neonates, 21 belongs to sepsis; 14 to probable sepsis; 65 to no sepsis. HSS in umbilical cord blood (UCB) had Sensitivity-74.28%, Specificity-92.30%, PPV-83.87%, NPV-86.95% and HSS in PVB had Sensitivity-62.85%, Specificity- 87.69%, PPV-75.86%, NPV-81.69%. Conclusion: HSS score in UCB can be used as a simple, quick, cost-effective, and readily available screening test with decent sensitivity and high specificity, for the detection of EONS.

Bacteria profiles and risk factors for proven early-onset sepsis in preterm neonates.

Objectives:To fill this gap in the literature and establish a prediction model.Methods:This retrospective study was conducted in a Neonatal Intensive Care Unit between April 2018 and April 2019. Sixty-five sepsis cases were clinically diagnosed with early-onset neonatal sepsis (EONS) and confirmed by bacterial culture, and 91 newborns were enrolled as control. Multivariate analysis was used to analyze the data, and the predictive efficiency of the prediction model was verified using the Hosmer-Lemeshow goodness-of-fit test and receiver operating characteristic (ROC) curve.Results:There were differences in multiple gestation birth, cesarean section, gestational age, birth weight, Apgar scores at 1 and 5 minutes, and laboratory parameters including white blood cells, neutrophils, lymphocytes, platelets, C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6) between the groups. Multivariable logistic analysis showed that the Apgar score at 5 minutes and CRP, PCT, and IL-6 levels remained independent significant predictors of EONS (p=0.002, p=0.020, p=0.002, p=0.021, respectively). According to multivariate logistic regression analysis, the risk prediction model was logit p=24.280–3.270 x Apgar score at 5 minutes + 1.396 x CRP + 3.409 x PCT + 0.034 x IL-6 (Lemeshow goodness-of-fit test p=0.143). Receiver operating characteristic curve analysis indicated that the area under the curve was 0.968 (95% confidence interval: 0.936–1.000, p<0.05), and the sensitivity was 90.8% and specificity was 97.8%.Conclusion:The Apgar score at 5 minutes and CRP, PCT, and IL-6 levels are risk factors for EONS. The risk prediction model is highly efficient in predicting EONS among preterm infants.

EVALUATION OF CORD BLOOD CULTURE AS AN EARLY PREDICTOR FOR THE DETECTION OF EARLY ONSET NEONATAL SEPSIS IN TERTIARY CENTRE OF CENTRAL INDIA.

BACKGROUND : Neonatal sepsis is one of the major causes of neonatal morbidity and mortality. Peripheral venous blood culture and sensitivity is gold standard for the diagnosis of neonatal sepsis. Low sensitivity of blood culture in newborn is due to small volume of blood sample collected from neonates &amp; antibiotics given before sampling. AIM : To evaluate the utility &amp; compare the Umblical cord blood culture(UCBC) with Peripheral venous blood culture(PVBC) for detection of Early Onset Neonatal Sepsis(EONS) METHOD : 100 inborn neonates with two or more risk factors for EONS, chosen by sequential sampling method were included in this prospective analytical study. Blood samples were collected from umbilical cord and peripheral vein for culture. Sepsis screen was done to corroborate the diagnosis of neonatal sepsis. RESULT : Out of 100 neonates, 21 belongs to sepsis; 14 to probable sepsis; 65 to no sepsis. UCBC had Sensitivity-65.71% , Specicity-93.84%, PPV-85.18% , NPV-83.56% &amp; PVBC had Sensitivity-60% , Specicity-95.38% , PPV-87.5% , NPV-81.57%. CONCLUSION : UCBC is simple and convenient method for the diagnosis of EONS compared to PVBC. Organisms grown are comparable to PVBC sample.

The Relationship Among Intra-Amniotic Inflammatory Response, The Progression of Inflammation in Chorionic Plate and Early-Onset Neonatal Sepsis.

Background: The chorionic plate (CP) has been denigrated by the well-known route of the extraplacental membranes from the decidua parietalis through the chorion to the amnion in the progression of ascending intrauterine infection among preterm births (PTBs). However, considering previous studies reporting the relationship among intra-amniotic inflammatory response (IAIR), the progression of inflammation in extraplacental membranes and early-onset neonatal sepsis (EONS), and the anatomic connection between extraplacental membranes and CP, there is a good chance that IAIR would be more likely and severe according to the progression of inflammation in CP, and this progression of inflammation in CP would be associated with a significant increase in EONS in neonates delivered due to either PTL or preterm-PROM. Unfortunately, there is no information about the relationship among IAIR, the progression of inflammation in CP, and EONS among spontaneous PTBs. The objective of the current study is to examine this issue.Method: The study population included 309 singleton pregnant women-delivered preterm neonates with the following conditions: (1) gestational age (GA) at delivery: 20.0~36.9 weeks; (2) spontaneous PTBs: PTL (151 cases) or preterm-PROM (158 cases); (3) available results of placental histologic examination; (4) without congenital anomaly; and (5) delivery within 60 h of amniocentesis. We examined IAIR, and the frequency of intra-amniotic inflammation (IAI) and EONS according to the progression of inflammation in CP [i.e., stage-0, inflammation-free CP; stage-1, inflammation restricted to subchorionic fibrin (SCF); stage-2, inflammation in connective tissue (CT) of CP but without chorionic vasculitis; and stage-3, chorionic vasculitis]. IAIR was determined by amniotic fluid (AF) matrix metalloproteinase-8 (MMP-8) concentration (ng/ml), and IAI was defined as an elevated AF MMP-8 concentration (≥23 ng/ml). EONS included either suspected or proven EONS.Results: (1) Each stage (stage-0 to stage-3) was present in 69.3% (214/309), 15.9% (49/309), 11.0% (34/309), and 3.9% (12/309) of the study population. (2) AF MMP-8 concentrations continuously elevated according to the progression of inflammation in CP [stage-0 vs. stage-1 vs. stage-2 vs. stage-3; median (ng/ml), range (ng/ml); 6.0 (0.3–4202.7) vs. 153.9 (0.3–6142.6) vs. 464.9 (5.8–3929.0) vs. 1,780.4 (35.1–5019.5); Kruskal–Wallis test, P < 0.001 and Spearman's rank-correlation test, P < 0.000001, r = 0.553]. (3) Moreover, the frequency of IAI and EONS gradually increased with the progression of inflammation in CP [stage-0 vs. stage-1 vs. stage-2 vs. stage-3; IAI, 30.5% (64/210) vs. 70.2% (33/47) vs. 96.7% (29/30) vs. 100% (12/12); EONS, 3.5% (7/200) vs. 25.5% (12/47) vs. 32.3% (10/31) vs. 40.0% (4/10); each for Pearson's chi-square test, P < 0.000001 and linear-by-linear association, P < 0.000001]. (4) Of note, multiple logistic regression analysis demonstrated that a more advanced stage in the progression of inflammation within CP was associated with a higher odds ratio (OR) for EONS [stage-1 vs. stage-2 vs. stage-3; OR, 7.215, 95% confidence-interval (CI) (2.177–23.908) vs. OR, 10.705, 95% CI (2.613–43.849) vs. OR, 27.189, 95% CI (2.557–289.124)] compared with stage-0 even after the adjustment for potential confounding variables.Conclusion: IAIR is more likely and severe according to the progression of inflammation in CP, and this progression of inflammation in CP is an independent risk factor for EONS in spontaneous PTBs. This finding suggests that CP may be another playground for the progression of ascending intrauterine infection in addition to extraplacental membranes, and the progression of inflammation in CP may be used for the prediction of EONS in spontaneous PTBs.

Early-Onset Neonatal E. coli Sepsis in Term Infants in the Absence of Antenatal or Intrapartum Risk Factors for Infection

Early-onset neonatal sepsis (EONS), an important cause of neonatal morbidity and mortality, is usually due to ascending infection from maternal genital tract or infected amniotic fluid. The most common organism is group B streptococcus (GBS), followed by Esc herichia coli (E. coli). Risk factors include maternal GBS colonization, chorioamnionitis, prolonged membrane rupture, prematurity, and intrapartum maternal pyrexia. The presentation of EONS can be varied, ranging from temperature instability to profound hypotension. We present two cases of E. coli EONS in term infants presenting as respiratory distress, without risk factors for infection. The first case is a 34-year-old female, with history of one previous caesarean section (CS), who underwent a repeat CS at 37+1 week’s gestation for obstetric cholestasis. Investigations performed on the second day of neonatal life in view of persistent respiratory distress, revealed E. coli bacteremia, complicated by septic shock. The mother developed fever on the first post-operative day due to E. coli bacteremia. The second case is a 31-year-old GBS negative primigravida with gestational diabetes, who underwent an induction of labor at 38+ 3 weeks. She had a forceps delivery for fetal distress six hours after membrane rupture. On the second day of life, the neonate had retractions and poor feeding, and blood cultures grew E. coli. There were no risk factors for EONS. The neonate rapidly deteriorated and despite extracorporeal membrane oxygenation, passed away on the seventh day of life. These cases illustrate the importance of E. coli as a cause of EONS and the need for a high index of suspicion due to the subtle presentation. Prompt recognition and treatment are important even in the absence of risk factors, as there is potential for rapid deterioration if treatment is delayed. In the presence of definite risk factors, broad-spectrum antibiotics should be considered for E. coli and GBS.

The risk of early-onset neonatal sepsis in preterm infants with maternal histologic chorioamnionitis

Background Chorioamnionitis, usually a subclinical condition, maycause preterm delivery and long-term morbidity.Objective The objective of this study was to determine the risk ofearly-onset neonatal sepsis in preterm infants with maternal histo-logic chorioamnionitis (HCA).Methods This was a prospective cohort study of preterm infantsborn at Sanglah Hospital, Denpasar from September 2002 to Feb-ruary 2004. Histopathological examinations of the subjects’ placen-tas were done and the infants were monitored for 72 hours for clini-cal signs of early-onset neonatal sepsis. Maternal and neonatal riskfactors were analyzed using multivariate statistical analysis.Results Eighty-two preterm infants were included, of which 41 werepositive for maternal HCA. Twenty-five (61%) of the infants posi-tive for maternal HCA developed early-onset neonatal sepsis, com-pared to 5 (12%) of those negative for maternal HCA (RR=5, 95%CI2.12;11.78). Nine infants died from early onset neonatal sepsis.Eight of them had positive HCA, and only one had negative HCA.The average length of hospital stay between infants with and with-out maternal HCA did not differ significantly [12.0 (SD 5.08) vs.12.6 (SD 1.34); P=0.80]. Logistic regression model analysis iden-tified only HCA as a significant risk factor for early-onset neonatalsepsis (OR=6.9, 95%CI 2.0;23). Gestational age (OR=1.3, 95%CI0.8;2.0), birth weight (OR=1.0, 95%CI 0.9;1.0), and neonatal as-phyxia (OR=1.0, 95%CI 0.1;4.4) were not found to be significantrisk factors.Conclusion Preterm infants with maternal histologicchorioamnionitis are at a higher risk for developing early-onsetneonatal sepsis

Utility of cord blood culture in early onset neonatal sepsis.

Neonatal sepsis is a major cause of neonatal mortality. The clinical outcome mainly depends on the early diagnosis and peripheral venous blood culture (PVBC) is the most widely practiced diagnostic method. This study aimed to evaluate the utility of umbilical cord blood culture (UCBC) in neonates at high risk of early onset neonatal sepsis (EONS) in comparison to peripheral venous blood culture. A total of 40 neonates with two or more risk factors for EONS were included in the study. Umbilical cord blood was collected aseptically during delivery for blood culture and C-reactive protein (CRP). Peripheral venous blood was collected within 24 hours of birth for sepsis screen and PVBC. Although 11 babies were sepsis screen positive, cord blood CRP was negative in all cases. In comparison to PVBC, UCBC had 100 per cent sensitivity and 94.9 per cent specificity. The results of UCBC were consistent with PVBC. One neonate who was both UCBC and PVBC positive also had isolation of the same pathogen in both the cultures and 33 per cent PPV for UCBC. UCBC is a simple convenient method, which ensures culture of adequate volume of blood from newborns allowing effective early isolation of bacterial pathogens, especially in EONS.

Reduction in the use of diagnostic tests in infants with risk factors for early-onset neonatal sepsis does not delay antibiotic treatment.

Despite a low positive predictive value, diagnostic tests such as complete blood count (CBC) and C-reactive protein (CRP) are commonly used to evaluate whether infants with risk factors for early-onset neonatal sepsis (EOS) should be treated with antibiotics. We investigated the impact of implementing a protocol aiming at reducing the number of diagnostic tests in infants with risk factors for EOS in order to compare the diagnostic performance of repeated clinical examination with CBC and CRP measurement. The primary outcome was the time between birth and the first dose of antibiotics in infants treated for suspected EOS. Among the 11,503 infants born at ≥35 weeks during the study period, 222 were treated with antibiotics for suspected EOS. The proportion of infants receiving antibiotics for suspected EOS was 2.1% and 1.7% before and after the change of protocol (p = 0.09). Reduction of diagnostic tests was associated with earlier antibiotic treatment in infants treated for suspected EOS (hazard ratio 1.58; 95% confidence interval [CI] 1.20-2.07; p <0.001), and in infants with neonatal infection (hazard ratio 2.20; 95% CI 1.19-4.06; p = 0.01). There was no difference in the duration of hospital stay nor in the proportion of infants requiring respiratory or cardiovascular support before and after the change of protocol. Reduction of diagnostic tests such as CBC and CRP does not delay initiation of antibiotic treatment in infants with suspected EOS. The importance of clinical examination in infants with risk factors for EOS should be emphasised.